Heterocyclic sulfonamide derivative and medicine comprising same
Inventors
Kobayashi, Kaori • Suzuki, Tamotsu • Fujii, Tomohiro • Okuzumi, Tatsuya
Assignees
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Publication Number
US-10626112-B2
Publication Date
2020-04-21
Expiration Date
Abstract
The present invention provides a compound represented by the formula (I): wherein each symbol is as defined in the DESCRIPTION, or a pharmaceutically acceptable salt thereof. The compound has a superior TRPA1 antagonist activity, and can provide a medicament useful for the prophylaxis or treatment of diseases involving TRPA1 antagonist and TRPA1.
Core Innovation
The invention relates to compounds represented by formula (I) and pharmaceutically acceptable salts thereof. The compounds are defined through partial structures (a), (b), and (c), with Q being O or -O-, and with partial structure (b) containing ring A. The structural scope is constrained by k being 0 or 1, X being -Cy, Cy being any of the groups of the listed formulas, and R1, R4, and R5 being hydrogen.
Within partial structure (b), R6 is a cyclic C3-6 alkyl group optionally containing a hetero atom, and may also be a halogeno group, a C1-6 alkoxy group, a C1-6 alkoxycarbonyl group, an amino group, an amino group mono- or di-substituted by a C1-6 alkyl group, or a hydroxy group. The disclosed structural space includes monocyclic or bicyclic aromatic or heteroaromatic ring systems, sulfonyl-linked and carboxamide-related motifs, and fluorinated or other substituted ring variations.
The partial content also describes specific compound examples and reference structures with fluorobenzofuran, sulfonyl, pyrrolidine-2-carboxamide, pyrrolidine, azetidine, azabicyclo[2.2.1]heptane, pyridine, pyrimidine, pyrazine, and related heteroaryl substituents. These examples include stereochemical variants such as 2S configurations and substituted aryl or heteroaryl groups, while remaining within the general formula (I) framework.
Claims Coverage
The claim coverage centers on one independent compound claim for formula (I), together with dependent coverage that refines the structural scope and adds pharmaceutical composition and TRPA1-associated disease treatment uses. The independent claim includes the core inventive features of the formula (I) scaffold, the partial structures (a), (b), and (c), and the fixed hydrogen substituents at R1, R4, and R5.
Formula (I) compound with constrained partial structures
A compound represented by formula (I), wherein Q is O or -O-, partial structures (a), (b), and (c) are defined by the listed formulas, partial structure (b) contains ring A, and the compound is provided as a pharmaceutically acceptable salt thereof.
Ring A substituent pattern via (R6)k and X = -Cy
Partial structure (b) contains ring A, where k is 0 or 1, R6 is a cyclic C3-6 alkyl group optionally containing a hetero atom or one of the listed halogeno, alkoxy, alkoxycarbonyl, amino, substituted amino, or hydroxy groups, X is -Cy, and Cy is any of the groups of the listed formulas.
Hydrogen constraints on R1, R4, and R5
The compound of formula (I) specifies that R1 is hydrogen, R4 is hydrogen, and R5 is hydrogen.
Pharmaceutical composition with pharmaceutically acceptable carriers
A pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt together with one or more pharmaceutically acceptable carriers.
Treatment of TRPA1-associated disease by administering an effective amount
A method treating a TRPA1-associated disease by administering to a subject in need an effective amount of the compound or a pharmaceutically acceptable salt.
Overall, the claim coverage is directed to a formula (I) compound family defined by partial structures (a), (b), and (c), with ring A constrained through the (R6)k and X = -Cy pattern and with R1, R4, and R5 fixed as hydrogen. The dependent coverage extends to pharmaceutical compositions and to treatment of TRPA1-associated diseases by administration of an effective amount.
Stated Advantages
Inhibits and/or down-regulates TRPA1 activation, associated with reduced intracellular Ca2+ influx.
Provides prophylaxis and/or treatment of TRPA1-involving diseases across multiple disease areas including pain, digestive tract diseases, lung diseases, bladder diseases, inflammatory diseases, dermatologic diseases, and neurological diseases.
Superior TRPA1 antagonist activity.
Useful for prophylaxis and treatment of TRPA1-involving diseases.
Documented Applications
Treatment of TRPA1-associated disease by administering an effective amount of the compound or a pharmaceutically acceptable salt to a subject in need.
Prophylaxis or treatment of TRPA1-associated diseases using the compound or a pharmaceutically acceptable salt.
Medicaments for TRPA1-associated diseases.
TRPA1-associated disease indications explicitly listed include chronic pain, acute pain, diabetic neuropathy, osteoarthritis, asthma, chronic coughing, chronic obstructive pulmonary disease, functional gastrointestinal disorder, reflux esophagitis, irritable bowel syndrome, inflammatory bowel disease, pancreatitis, anticancer agent-induced neuropathy, pruritus, and allergic dermatitis.
Prophylaxis and treatment of TRPA1-involving diseases.
Treatment of pain-associated diseases, digestive tract diseases, lung diseases, bladder diseases, inflammatory diseases, dermatic diseases, and neurological diseases.
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